A Computational Framework for the Administration of 5-Aminovulinic Acid Before Glioblastoma Surgery.

5-Aminolevulinic Acid (5-ALA) is the only fluorophore approved by the FDA as an intraoperative optical imaging agent for fluorescence-guided surgery in patients with glioblastoma. The dosing regimen is based on rodent tests where a maximum signal occurs around 6 h after drug administration. Here, we construct a computational framework to simulate the transport of 5-ALA through the stomach, blood, and brain, and the subsequent conversion to the fluorescent agent protoporphyrin IX at the tumor site. The framework combines compartmental models with spatially-resolved partial differential equations, enabling one to address questions regarding quantity and timing of 5-ALA administration before surgery. Numerical tests in two spatial dimensions indicate that, for tumors exceeding the detection threshold, the time to peak fluorescent concentration is 2-7 h, broadly consistent with the current surgical guidelines. Moreover, the framework enables one to examine the specific effects of tumor size and location on the required dose and timing of 5-ALA administration before glioblastoma surgery.

Prognostic relevance of radiological findings on early postoperative MRI for 187 consecutive glioblastoma patients receiving standard therapy.

Several prognostic factors are known to influence survival for patients treated with IDH-wildtype glioblastoma, but unknown factors may remain. We aimed to investigate the prognostic implications of early postoperative MRI findings. A total of 187 glioblastoma patients treated with standard therapy were consecutively included. Patients either underwent a biopsy or surgery followed by an early postoperative MRI. Progression-free survival (PFS) and overall survival (OS) were analysed for known prognostic factors and MRI-derived candidate factors: resection status as defined by the response assessment in neuro-oncology (RANO)-working group (no contrast-enhancing residual tumour, non-measurable contrast-enhancing residual tumour, or measurable contrast-enhancing residual tumour) with biopsy as reference, contrast enhancement patterns (no enhancement, thin linear, thick linear, diffuse, nodular), and the presence of distant tumours. In the multivariate analysis, patients with no contrast-enhancing residual tumour or non-measurable contrast-enhancing residual tumour on the early postoperative MRI displayed a significantly improved progression-free survival compared with patients receiving only a biopsy. Only patients with non-measurable contrast-enhancing residual tumour showed improved overall survival in the multivariate analysis. Contrast enhancement patterns were not associated with survival. The presence of distant tumours was significantly associated with both poor progression-free survival and overall survival and should be considered incorporated into prognostic models.

Association of 5-aminolevulinic acid fluorescence guided resection with photodynamic therapy in recurrent glioblastoma: a matched cohort study.

PURPOSE: Glioblastoma is a malignant and aggressive brain tumour that, although there have been improvements in the first line treatment, there is still no consensus regarding the best standard of care (SOC) upon its inevitable recurrence. There are novel adjuvant therapies that aim to improve local disease control. Nowadays, the association of intraoperative photodynamic therapy (PDT) immediately after a 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) in malignant gliomas surgery has emerged as a potential and feasible strategy to increase the extent of safe resection and destroy residual tumour in the surgical cavity borders, respectively. OBJECTIVES: To assess the survival rates and safety of the association of intraoperative PDT with 5-ALA FGR, in comparison with a 5-ALA FGR alone, in patients with recurrent glioblastoma. METHODS: This article describes a matched-pair cohort study with two groups of patients submitted to 5-ALA FGR for recurrent glioblastoma. Group 1 was a prospective series of 11 consecutive cases submitted to 5-ALA FGR plus intraoperative PDT; group 2 was a historical series of 11 consecutive cases submitted to 5-ALA FGR alone. Age, sex, Karnofsky performance scale (KPS), 5-ALA post-resection status, T1-contrast-enhanced extent of resection (EOR), previous and post pathology, IDH (Isocitrate dehydrogenase), Ki67, previous and post treatment, brain magnetic resonance imaging (MRI) controls and surgical complications were documented. RESULTS: The Mantel-Cox test showed a significant difference between the survival rates (p = 0.008) of both groups. 4 postoperative complications occurred (36.6%) in each group. As of the last follow-up (January 2024), 7/11 patients in group 1, and 0/11 patients in group 2 were still alive. 6- and 12-months post-treatment, a survival proportion of 71,59% and 57,27% is expected in group 1, versus 45,45% and 9,09% in group 2, respectively. 6 months post-treatment, a progression free survival (PFS) of 61,36% and 18,18% is expected in group 1 and group 2, respectively. CONCLUSION: The association of PDT immediately after 5-ALA FGR for recurrent malignant glioma seems to be associated with better survival without additional or severe morbidity. Despite the need for larger, randomized series, the proposed treatment is a feasible and safe addition to the reoperation.

Prognostic value of preoperative diffusion restriction in glioblastoma.

INTRODUCTION: Although glioblastoma (GBM) has a very poor prognosis, overall survival (OS) in treated patients shows great difference varying from few days to several months. Identifying factors explaining this difference would improve management of patient treatment. AIM: To determine the relevance of diffusion restriction in newly diagnosed treatment-naïve GBM patients. METHODS: Preoperative magnetic resonance scans of 33 patients with GBM were reviewed. Regions of interest including all the T2 hyperintense lesion were drawn on diffusion weighted B0 images and transferred to the apparent diffusion coefficient (ADC) map. For each patient, a histogram displaying the ADC values within in the regions of interest was generated. Volumetric parameters including tumor regions with restricted diffusion, parameters derived from histogram and mean ADC value of the tumor were calculated. Their relationship with OS was analyzed. RESULTS: Patients with mean ADC value < 1415x10-6 mm2/s had a significantly shorter OS (p=0.021). Among volumetric parameters, the percentage of volume within T2 lesion with a normalized ADC value <1.5 times that in white matter was significantly associated with OS (p=0.0045). Patients with a percentage>23.92% had a shorter OS. Among parameters derived from histogram, the 50th percentile showed a trend towards significance for OS (p=0.055) with patients living longer when having higher values of 50th percentile. A difference in OS was observed between patients according to ADC peak of histogram but this difference did not reach statistical significance (p=0.0959). CONCLUSION: Diffusion magnetic resonance imaging may provide useful information for predicting GBM prognosis.

Results from a first-in-human phase I safety trial to evaluate the use of a vascularized pericranial/temporoparietal fascial flap to line the resection cavity following resection of newly diagnosed glioblastoma.

PURPOSE: The efficacy of systemic therapies for glioblastoma (GBM) remains limited due to the constraints of systemic toxicity and blood-brain barrier (BBB) permeability. Temporoparietal fascial flaps (TPFFs) and vascularized peri cranial flaps (PCF) are not restricted by the blood-brain barrier (BBB), as they derive their vascular supply from branches of the external carotid artery. Transposition of a vascularized TPFF or PCF along a GBM resection cavity may bring autologous tissue not restricted by the BBB in close vicinity to the tumor bed microenvironment, permit ingrowth of vascular channels fed by the external circulation, and offer a mechanism of bypassing the BBB. In addition, circulating immune cells in the vascularized flap may have better access to tumor-associated antigens (TAA) within the tumor microenvironment. We conducted a first-in-human Phase I trial assessing the safety of lining the resection cavity with autologous TPFF/PCF of newly diagnosed patients with GBM. METHODS: 12 patients underwent safe, maximal surgical resection of newly diagnosed GBMs, followed by lining of the resection cavity with a pedicled, autologous TPFF or PCF. Safety was assessed by monitoring adverse events. Secondary analysis of efficacy was examined as the proportion of patients experiencing progression-free disease (PFS) as indicated by response assessment in neuro-oncology (RANO) criteria and overall survival (OS). The study was powered to determine whether a Phase II study was warranted based on these early results. For this analysis, subjects who were alive and had not progressed as of the date of the last follow-up were considered censored and all living patients who were alive as of the date of last follow-up were considered censored for overall survival. For simplicity, we assumed that a 70% PFS rate at 6 months would be considered an encouraging response and would make an argument for further investigation of the procedure. RESULTS: Median age of included patients was 57 years (range 46-69 years). All patients were Isocitrate dehydrogenase (IDH) wildtype. Average tumor volume was 56.6 cm3 (range 14-145 cm3). Resection was qualified as gross total resection (GTR) of all of the enhancing diseases in all patients. Grade III or above adverse events were encountered in 3 patients. No Grade IV or V serious adverse events occurred in the immediate post-operative period including seizure, infection, stroke, or tumor growing along the flap. Disease progression at the site of the original tumor was identified in only 4 (33%) patients (median 23 months, range 8-25 months), 3 of whom underwent re-operation. Histopathological analyses of those implanted flaps and tumor bed biopsy at repeat surgery demonstrated robust immune infiltrates within the transplanted flap. Importantly, no patient demonstrated evidence of tumor infiltration into the implanted flap. At the time of this manuscript preparation, only 4/12 (33%) of patients have died. Based on the statistical considerations above and including all 12 patients 10/12 (83.3%) had 6-month PFS. The median PFS was 9.10 months, and the OS was 17.6 months. 4/12 (33%) of patients have been alive for more than two years and our longest surviving patient currently is alive at 60 months. CONCLUSIONS: This pilot study suggests that insertion of pedicled autologous TPFF/PCF along a GBM resection cavity is safe and feasible. Based on the encouraging response rate in 6-month PFS and OS, larger phase II studies are warranted to assess and reproduce safety, feasibility, and efficacy. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: ClinicalTrials.gov ID NCT03630289, dated: 08/02/2018.

Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies.

Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of patients with glioblastoma remains a considerable challenge due to the infiltrative nature of the tumor, rapid growth rates, and tumor heterogeneity. Standard therapy consists of maximally safe microsurgical resection followed by adjuvant radio- and chemotherapy with temozolomide. In recent years, local therapies have been extensively investigated in experimental as well as translational levels. External stimuli-responsive therapies such as Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT) and Radiodynamic Therapy (RDT) can induce cell death mechanisms via generation of reactive oxygen species (ROS) after administration of five-aminolevulinic acid (5-ALA), which induces the formation of sensitizing porphyrins within tumor tissue. Preliminary data from clinical trials are available. The aim of this review is to summarize the status of such therapeutic approaches as an adjunct to current standard therapy in glioblastoma.

SUPRAMAX-study: supramaximal resection versus maximal resection for glioblastoma patients: study protocol for an international multicentre prospective cohort study (ENCRAM 2201).

INTRODUCTION: A greater extent of resection of the contrast-enhancing (CE) tumour part has been associated with improved outcomes in glioblastoma. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in high-grade glioma (HGG) patients in terms of survival, functional, neurological, cognitive and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively. METHODS AND ANALYSIS: This study is an international, multicentre, prospective, two-arm cohort study of observational nature. Consecutive glioblastoma patients will be operated with SMR or maximal resection at a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months postoperatively. Secondary endpoints are (1) residual CE and NCE tumour volume on postoperative T1-contrast and FLAIR (Fluid-attenuated inversion recovery) MRI scans; (2) progression-free survival; (3) receipt of adjuvant therapy with chemotherapy and radiotherapy; and (4) quality of life at 6 weeks, 3 months and 6 months postoperatively. The total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment.

Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.

Radiological and Not Clinical Variables Guide the Surgical Plan in Patients with Glioblastoma.

Background and Purpose: The extent of resection is the most important prognostic factor in patients with glioblastoma. However, the factors influencing the decision to perform a biopsy instead of maximal resection have not been clearly established. The aim of this study was to analyze the factors associated with the intention to achieve maximal resection in glioblastoma patients. Methods: A retrospective single-center case-series analysis of patients with a new diagnosis of glioblastoma was performed. Patients were distributed into two groups: the biopsy (B) and complete resection (CR) groups. To identify factors associated with the decision to perform a B or CR, uni- and multivariate binary logistic regression analyses were performed. Cox regression analysis was also performed in the B and CR groups. Results: Ninety-nine patients with a new diagnosis of glioblastoma were included. Sixty-eight patients (68.7%) were treated with CR. Ring-enhancement and edema volume on presurgical magnetic resonance imaging were both associated with CR. Corpus callosum involvement and proximity to the internal capsule were identified as factors associated with the decision to perform a biopsy. In the multivariate analysis, edema volume (OR = 1.031; p = 0.002) and proximity to the internal capsule (OR = 0.104; p = 0.001) maintained significance and were considered independent factors. In the survival analysis, only corpus callosum involvement (HR = 2.055; p = 0.035) and MGMT status (HR = 0.484; p = 0.027) presented statistical significance in the CR group. Conclusions: The volume of edema and proximity to the internal capsule were identified as independent factors associated with the surgical decision. The radiological evaluation and not the clinical situation of the patient influences the decision to perform a biopsy or CR.

Supramaximal resection: retrospective study on IDH-wildtype Glioblastomas based on the new RANO-Resect classification.

BACKGROUND: The prognostic value of the extent of resection in the management of Glioblastoma is a long-debated topic, recently widened by the 2022 RANO-Resect Classification, which advocates for the resection of the non-enhancing disease surrounding the main core of tumors (supramaximal resection, SUPR) to achieve additional survival benefits. We conducted a retrospective analysis to corroborate the role of SUPR by the RANO-Resect Classification in a single center, homogenous cohort of patients. METHODS: Records of patients operated for WHO-2021 Glioblastomas at our institution between 2007 and 2018 were retrospectively reviewed; volumetric data of resected lesions were computed and classified by RANO-Resect criteria. Survival and correlation analyses were conducted excluding patients below near-total resection. RESULTS: 117 patients met the inclusion criteria, encompassing 45 near-total resections (NTR), 31 complete resections (CR), and 41 SUPR. Median progression-free and overall survival were 11 and 15 months for NTR, 13 and 17 months or CR, 20 and 24 months for SUPR, respectively (p < 0.001), with inverse correlation observed between survival and FLAIR residual volume (r -0.28). SUPR was not significantly associated with larger preoperative volumes or higher rates of postoperative deficits, although it was less associated with preoperative neurological deficits (OR 3.37, p = 0.003). The impact of SUPR on OS varied between MGMT unmethylated (HR 0.606, p = 0.044) and methylated (HR 0.273, p = 0.002) patient groups. CONCLUSIONS: Results of the present study support the validity of supramaximal resection by the new RANO-Resect classification, also highlighting a possible surgical difference between tumors with methylated and unmethylated MGMT promoter.

Intraoperative ultrasound for surgical resection of high-grade glioma and glioblastoma: a meta-analysis of 732 patients.

PURPOSE: Here, we conducted a meta-analysis to explore the use of intraoperative ultrasound (iUS)-guided resection in patients diagnosed with high-grade glioma (HGG) or glioblastoma (GBM). Our aim was to determine whether iUS improves clinical outcomes compared to conventional neuronavigation (CNN). METHODS: Databases were searched until April 21, 2023 for randomized controlled trials (RCTs) and observational cohort studies that compared surgical outcomes for patients with HGG or GBM with the use of either iUS in addition to standard approach or CNN. The primary outcome was overall survival (OS). Secondary outcomes include volumetric extent of resection (EOR), gross total resection (GTR), and progression-free survival (PFS). Outcomes were analyzed by determining pooled relative risk ratios (RR), mean difference (MD), and standardized mean difference (SMD) using random-effects model. RESULTS: Of the initial 867 articles, only 7 articles specifically met the inclusion criteria (1 RCT and 6 retrospective cohorts). The analysis included 732 patients. Compared to CNN, the use of iUS was associated with higher OS (SMD = 0.26,95%CI=[0.12,0.39]) and GTR (RR = 2.02; 95% CI=[1.31,3.1]) for both HGG and GBM. There was no significant difference in PFS or EOR. CONCLUSION: The use of iUS in surgical resections for HGG and GBM can improve OS and GTR compared to CNN, but it did not affect PFS. These results suggest that iUS reduces mortality associated with HGG and GBM but not the risk of recurrence. These results can provide valuable cost-effective interventions for neurosurgeons in HGG and GBM surgery.

Multiple surgical resections for progressive IDH wildtype glioblastoma-is it beneficial?

PURPOSE: The role of repeat resection for recurrent glioblastoma (rGB) remains equivocal. This study aims to assess the overall survival and complications rates of single or repeat resection for rGB. METHODS: A single-centre retrospective review of all patients with IDH-wildtype glioblastoma managed surgically, between January 2014 and January 2022, was carried out. Patient survival and factors influencing prognosis were analysed, using Kaplan-Meier and Cox regression methods. RESULTS: Four hundred thirty-two patients were included, of whom 329 underwent single resection, 83 had two resections and 20 patients underwent three resections. Median OS (mOS) in the cohort who underwent a single operation was 13.7 months (95% CI: 12.7-14.7 months). The mOS was observed to be extended in patients who underwent second or third-time resection, at 22.9 months and 44.7 months respectively (p < 0.001). On second operation achieving > 95% resection or residual tumour volume of < 2.25 cc was significantly associated with prolonged survival. There was no significant difference in overall complication rates between primary versus second (p = 0.973) or third-time resections (p = 0.312). The use of diffusion tensor imaging (DTI) guided resection was associated with reduced post-operative neurological deficit (RR 0.37, p = 0.002), as was use of intraoperative ultrasound (iUSS) (RR 0.45, p = 0.04). CONCLUSIONS: This study demonstrates potential prolongation of survival for rGB patients undergoing repeat resection, without significant increase in complication rates with repeat resections. Achieving a more complete repeat resection improved survival. Moreover, the use of intraoperative imaging adjuncts can maximise tumour resection, whilst minimising the risk of neurological deficit.

The detrimental effect of biopsy preceding resection in surgically accessible glioblastoma: results from the national cancer database.

PURPOSE: Aggressive resection in surgically-accessible glioblastoma (GBM) correlates with improved survival over less extensive resections. However, the clinical impact of performing a biopsy before definitive resection have not been previously evaluated. METHODS: We analyzed 17,334 GBM patients from the NCDB from 2010-2014. We categorized them into: "upfront resection" and "biopsy followed by resection". The outcomes of interes included OS, 30-day readmission/mortality, 90-day mortality, and length of hospital stay (LOS). The Kaplan-Meier methods and accelerated failure time (AFT) models were applied for survival analysis. Multivariable binary logistic regression were performed to compare differences among groups. Multiple imputation and propensity score matching (PSM) were conducted for validation. RESULTS: "Upfront resection" had superior OS over "biopsy followed by resection" (median OS:12.4 versus 11.1 months, log-rank p = 0.001). Similarly, multivariable AFT models favored "upfront resection" (time ratio[TR]:0.83, 95%CI: 0.75-0.93, p = 0.001). Patients undergoing "upfront gross-total resection (GTR)" had higher OS over "upfront subtotal resection (STR)", "GTR following STR", and "GTR or STR following initial biopsy" (14.4 vs. 10.3, 13.5, 13.3, and 9.1 months;TR: 1.00 [Ref.], 0.75, 0.82, 0.88, and 0.67). Recent years of diagnosis, higher income, facilities located in Southern regions, and treatment at academic facilities were significantly associated with the higher likelihood of undergoing upfront resection. Multivariable regression showed a decreased 30 and 90-day mortality for patients undergoing "upfront resection", 73% and 44%, respectively (p < 0.001). CONCLUSIONS: Pre-operative biopsies for surgically accessible GBM are associated with worse survival despite subsequent resection compared to patients undergoing upfront resection.

Adjuvant re-irradiation vs. no early re-irradiation of resected recurrent glioblastoma: pooled comparative cohort analysis from two tertiary centers.

BACKGROUND: The optimal management strategy for recurrent glioblastoma (rGBM) remains uncertain, and the impact of re-irradiation (Re-RT) on overall survival (OS) is still a matter of debate. This study included patients who achieved gross total resection (GTR) after a second surgery after recurrence, following the GlioCave criteria. METHODS: Inclusion criteria include being 18 years or older, having histologically confirmed locally recurrent IDHwt or IDH unknown GBM, achieving MRI-proven GTR after the second surgery, having a Karnofsky performance status of at least 60% after the second surgery, having a minimum interval of 6 months between the first radiotherapy and the second surgery, and a maximum of 8 weeks from second surgery to the start of Re-RT. RESULTS: A total of 44 patients have met the inclusion criteria. The median OS after the second surgery was 14 months. All patients underwent standard treatment after initial diagnosis, including maximum safe resection, adjuvant radiochemotherapy and adjuvant chemotherapy. Re-RT did not significantly impact OS. However, MGMT promoter methylation status and a longer interval (> 12 months) between treatments were associated with better OS. Multivariate analysis revealed the MGMT status as the only significant predictor of OS. CONCLUSION: Factors such as MGMT promoter methylation status and treatment interval play crucial roles in determining patient outcomes after second surgery. Personalized treatment strategies should consider these factors to optimize the management of rGBM. Prospective research is needed to define the value of re-RT after second surgery and to inform decision making in this situation.

Hypofractionated stereotactic re-irradiation for progressive glioblastoma: twelve years' experience of a single center.

PURPOSE: We aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma. METHODS: The records of 77 previously irradiated glioblastoma patients who progressed and received second course hypofractionated SRT (1-5 fractions) between 2009 and 2022 in our department were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for all statistical analyses. RESULTS: The median time to progression from the end of initial radiotherapy was 14 months (range, 6-68 months). The most common SRT schedule was 30 Gy (range, 18-50 Gy) in 5 fractions (range, 1-5 fractions). The median follow-up after SRT was 9 months (range, 3-80 months). One-year overall (OS) and progression-free survival (PFS) rates after SRT were 46% and 35%, respectively. Re-irradiation dose and the presence of pseudoprogression were both significant independent positive prognostic factors for both OS (p = 0.009 and p = 0.04, respectively) and PFS (p = 0.008 and p = 0.04, respectively). For PFS, progression-free interval > 14 months was also a prognostic factor (p = 0.04). The treatment was well tolerated without significant acute toxicity. During follow-up, radiation necrosis was observed in 17 patients (22%), and 14 (82%) of them were asymptomatic. CONCLUSION: Hypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, received higher SRT doses, and experienced pseudoprogression following SRT had improved survival rates.

From Trauma to Tumor: Exploring Post-Traumatic Brain Injury Glioblastoma Patient Characteristics.

OBJECTIVE: Glioblastoma multiforme (GBM) following traumatic brain injury (TBI) is very rare and has not been comprehensively characterized by current literature. This systematic review aimed to characterize demographics of patients with post-TBI GBM. METHODS: A systematic review of case studies and case series was conducted for reports published up to April 2023. All case reports that satisfied the criteria for diagnosing post-TBI GBM were included. The JBI case report appraisal was used to assess the quality of reporting of included articles. RESULTS: Our review comprised 13 studies including 16 patients, most of whom were male (81%). Contusive TBI was the most frequent initial insult observed, with most patients requiring surgical intervention to manage TBI. The median latency between TBI and GBM diagnosis was 9.5 years with a negative correlation observed against patient age at TBI occurrence, but a positive correlation was noted for patients with IDH-wildtype GBM. Median age at GBM diagnosis was 56 years. CONCLUSIONS: This systematic review highlights a possible link to GBM development at the previous TBI site. Updated criteria for identifying post-TBI brain tumors are proposed to keep abreast with the latest advances in classifying central nervous system tumors. To establish a definitive link, a large-scale international multicenter study investigating the occurrence of World Health Organization grade IV IDH-wildtype de novo GBM after TBI is crucial. Regular monitoring, especially in middle-aged and older patients with TBI, is advisable.